In this study, we developed a cyclic peptide iRGD (CCRGDKGPDC)-conjugated solid lipid nanoparticle (SLN) to deliver small interfering RNAs (siRNAs) against both epidermal growth factor receptor (EGFR) and PD-L1 for combined targeted and immunotherapy against glioblastoma, the most aggressive type of brain tumors.
The developed multiscale model revealed angiogenesis-induced drug resistance mechanisms of brain tumors to EGFRI treatment and predicted a synergistic drug combination targeting both EGFR and VEGFR pathways with optimal combination timing.
Changes in expression of histone deacetylases (HDACs), which epigenetically regulate chromatin structure, and mutations and amplifications of the EGFR gene, which codes for the epidermal growth factor receptor (EGFR), have been reported in glioblastoma (GBM), the most common and malignant type of brain tumor.
Level 1: The use of afatinib is not recommended in patients with brain metastasis due to breast cancer.There is insufficient evidence to make recommendations regarding: the use of epidermal growth factor receptor inhibitors erlotinib and gefitinib in patients with brain metastasis due to nonsmall cell lung cancerthe use of BRAF inhibitors dabrafenib and vemurafenib in the treatment of patients with brain metastases due to metastatic melanomathe use of HER2 agents trastuzumab and lapatinib to treat patients with brain metastases due to metastatic breast cancerthe use of vascular endothelial growth factor agents bevacizumab, sunitinib, and sorafenib in the treatment of patients with solid tumor brain metastases.The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_9.
OBJECTIVE High-grade glial brain tumors are often characterized by an elevated expression of the tumorigenic epidermal growth factor receptor variant III ( EGFRvIII).
Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma.
This material architecture effectively delivers the EGFR kinase inhibitor Erlotinib (ERL) and Doxorubicin (DOX, DNA intercalator) in an ERL→DOX sequential manner to synergistically kill glioblastoma, the most aggressive form of brain cancer.
<b>Purpose:</b> The epidermal growth factor receptor variant III (<i>EGFRvIII</i>) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer.
Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group (<i>p</i><sub>gefitinib vs. erlotinib</sub>=0.995; <i>p</i><sub>gefitinib vs. icotinib</sub>=0.028; <i>p</i><sub>erlotinib vs. icotinib</sub>=0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors.
EGFRvIII, a variant of epidermal growth factor receptor (EGFR), is found in 20% of glioblastoma cases, which is the brain tumor with the highest malignancy.
Adoptive cell therapy (ACT) using T cells engineered with chimeric antigen receptor (CAR) targeting an ideal molecular marker in GBM, e.g. epidermal growth factor receptor type III (EGFRvIII) has demonstrated a satisfactory efficacy in treating malignant brain tumors.
EVs produced by specific brain tumor cell types may contain the corresponding oncogenic drivers, such as epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (and hence are often referred to as 'oncosomes').
In newly developed double tumor xenogeneic mouse models of brain metastasis this noninvasive method allowed differential diagnosis of HER2- and EGFR-expressing brain tumors.
The naturally secreted and O-GlcNAcylated MIF binds to EGFR, thereby inhibiting the binding of EGF to EGFR and EGF-induced EGFR activation, phosphorylation of ERK and c-Jun, cell invasion, proliferation and brain tumour formation.
In glioblastoma (GBM), a lethal form of brain cancer, the heterogeneous expression of the epidermal growth factor receptor (EGFR) poses a substantial challenge for the effective use of EGFR-targeted therapies.
Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells.
The mechanisms that drive therapeutic resistance to EGFR inhibitors in brain tumours are not well defined, and drug resistance contributes to the deadly and aggressive nature of the disease.
Here, human brain tumor-initiating cell (BTIC) lines with different combinations of endogenous EGFR wild-type, EGFRvIII, and PTEN mutations were used to investigate response to the EGFR inhibitor gefitinib, mTORC1 inhibitor rapamycin, and dual mTORC1/2 inhibitor AZD8055 alone and in combination with temozolomide (TMZ) EXPERIMENTAL DESIGN: In vitro growth inhibition and cell death induced by gefitinib, rapamycin, AZD8055, and TMZ or combinations in human BTICs were assessed by alamarBlue, neurosphere, and Western blotting assays.